RegulationAccelerated Approval (United States), Orphan Drug (United States), Orphan Drug (European Union), Conditional marketing approval (China), Priority Review (United States), Breakthrough Therapy (United States)

Structure/Sequence

Molecular FormulaC26H23N7O2

InChIKeyWDENQIQQYWYTPO-IBGZPJMESA-N

CAS Registry1420477-60-6

167

Clinical Trials associated with Acalabrutinib

NCT06520098

/ Not yet recruitingPhase 2IIT

Benefit of Venetoclax Addition ("Benefit VA") in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

People who have chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are often treated with ibrutinib, acalabrutinib, or zanubrutinib. These are pills that are taken by mouth. This type of pill is called "Bruton Tyrosine Kinase Inhibitor" or BTKi. Another treatment for CLL/SLL is a different pill called venetoclax.
The purpose of this study is to compare continuing the current treatment with BTKi alone, as long as it is working, to another arm of treatment which adds venetoclax to the current treatment (BTKi), for one year. After one year, both pills in this arm of treatment would be stopped and the participants will be closely monitored.

Start Date01 Jul 2025

Sponsor / Collaborator

VA Office of Research and Development

NCT06839872

/ Not yet recruitingPhase 2

BOSS: BTK Inhibitor Optimal Sequencing Study Phase II Open-label Single Arm Trial of Pirtobrutinib in Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma After First-line Acalabrutinib Progression

To assess the efficacy and safety of pirtobrutinib in participants with CLL/SLL who have progressed on first-line treatment with acalabrutinib.

Start Date30 Jun 2025

Sponsor / Collaborator

AstraZeneca PLC

[+1]

NCT06757647

/ RecruitingPhase 2IIT

Prospective Phase 2 Study of the Effect of Acalabrutinib on Myocardium on Ibrutinib Exposed Patients with CLL

This phase II trial tests how well acalabrutinib works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and evaluates how treatment with acalabrutinib affects heart function. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. CLL/SLL patients treated with a different BTK inhibitor called ibrutinib often experience cardiac side effects, leading to discontinuation of life-saving therapy. Treatment with acalabrutinib after discontinuing, or even before starting, treatment with ibrutinib may reverse or prevent cardiac side effects and be an effective treatment option for patients with CLL/SLL.

Start Date15 Mar 2025

Sponsor / Collaborator

Ohio State University Comprehensive Cancer Center

[+2]

100 Clinical Results associated with Acalabrutinib

100 Translational Medicine associated with Acalabrutinib

100 Patents (Medical) associated with Acalabrutinib

841

Literatures (Medical) associated with Acalabrutinib

01 Jun 2025·ANTI-CANCER DRUGS

BTK inhibitors enhance NKG2D ligand expression by regulating IL-10/STAT3 pathway in activated non-GCB diffuse large B-cell lymphoma cells

Article

Author: Jia, Zhu-xia ; Xiao, Bi-tao ; Qin, Wei ; Li, Jin ; Cai, Xiao-hui ; Zhou, Min ; Lu, Xu-zhang

The aim of this study is to explore the role of the IL-10/STAT3 pathway in the upregulation of natural killer group 2, member D (NKG2D) ligands (MICA and ULBP2) induced by Bruton’s tyrosine kinase (BTK) inhibitors in non-germinal center B-cell-like diffuse large B-cell lymphoma cells. The expression levels of NKG2D ligands and the IL-10/STAT3 pathway in SUDHL4, U2932, and OCI-LY3 cells were analyzed using western blotting. After stimulation of the B-cell receptor signaling pathway with IgM antibodies, the expression levels of NKG2D ligands, as well as IL-10 and phosphorylated STAT3 (p-STAT3) were significantly reduced. In contrast, treatment with ibrutinib produced effects opposite to those induced by IgM antibodies. Additionally, treatment of U2932 and OCI-LY3 cells with the STAT3 inhibitor (STAT3-IN-1) led to an increase in NKG2D ligand expression and a decrease in IL-10 levels. When IL-10 neutralizing antibodies were introduced, p-STAT3 levels decreased, and NKG2D ligand expression increased. Similar outcomes were observed when the BTK inhibitors ACP-196 and BGB-3111 were administered. Our findings suggest that the IL-10/STAT3 pathway plays a key role in the upregulation of NKG2D ligands induced by BTK inhibitors in U2932 and OCI-LY3 cells.

01 May 2025·ENVIRONMENTAL RESEARCH

Early life imidacloprid and copper exposure affects the gut microbiome, metabolism, and learning ability of honey bees (Apis mellifera)

Article

Author: Zhao, Chonghui ; Deng, Yi ; Pang, Yantao ; Fang, Richan ; Chen, Yuan ; Guo, Jun ; Tang, Qihe ; Chen, Yajuan ; Zhao, Yazhou ; Li, Xijie ; Li, Dan ; Li, Junjie ; Qian, Kai ; Hou, Mengshang ; Zhang, Jun

The pesticide imidacloprid and the heavy metal copper provide some degree of protection to plants, while at the same time causing varying degrees of damage to bees. However, few studies have investigated the negative effects of imidacloprid and copper exposure on newly emerged bees (young bees), especially when both are present in a mix. In this study, young bees were exposed to sterile sucrose solutions containing imidacloprid (10 μg/L, 100 μg/L), copper (10 mg/L, 50 mg/L), or a mix of both (10 μg/L + 10 mg/L) for 5 days to assess their gut system and behavior, with survival and dietary consumption recorded over 21 days. We found that imidacloprid and copper reduced honeybee survival, dietary intake, and learning ability, decreased gut microbiota diversity, and caused metabolic disruptions. Notably, the mix of imidacloprid and copper had a synergistic negative effect. Correlation analyses revealed that the honeybee gut microbiota influences bee immunity and behavior by regulating metabolic pathways related to ascorbate, tryptophan, and carbohydrates. Our results demonstrate that imidacloprid and copper, either alone or in a mix, alter young bee health through a complex mechanism of toxicity. These findings highlight imidacloprid and copper's negative effects on young honeybees, offering insights for future pesticide and heavy metal impact research.

01 May 2025·CLINICAL MICROBIOLOGY AND INFECTION

Fungal infection in patients treated with Bruton tyrosine kinase inhibitor—from epidemiology to clinical outcome: a systematic review

Review

Author: Gibert, Charles ; Blaize, Marion ; Fekkar, Arnaud

BACKGROUND:

The Bruton tyrosine kinase inhibitor (BTKi) has emerged as a key treatment for B-cell lymphomas. Despite its efficacy in the treatment of malignancies, numerous cases of invasive fungal infections (IFI) have been reported in patients receiving ibrutinib, a first-generation BTKi. Cases of invasive aspergillosis have also been reported with acalabrutinib and zanubrutinib.

OBJECTIVES:

The objective of this study was to provide an overview of the pathogens involved, the time of onset of infections and factors influencing survival.

METHODS:

Data sources: PubMed, Embase and Web of Science databases were used, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

STUDY ELIGIBILITY CRITERIA:

Case reports, case series, clinical trials and cohort studies were included.

PARTICIPANTS:

All reported cases of IFI in patients treated with BTKi were analysed. For case reports/case series, demographic, microbiological and outcome data were retrieved. Assessment of risk of bias: Given the significant heterogeneity in clinical trials/cohort studies, only epidemiological analysis was performed, without formal incidence analysis. Methods of data synthesis: Epidemiologic data were presented as descriptive statistics.

RESULTS:

In total, 25 215 patients from 92 retrospective and prospective clinical trials/cohort studies and 211 patients from 115 case reports/case series were included. Among clinical trials/cohorts, 736 IFI were reported, including 234 candidiasis (31.8%), 227 aspergillosis (30.8%) and 124 Pneumocystis jirovecii pneumonia (PJP) (16.8%). Among the case reports/case series, 155 (73.5%) had chronic lymphocytic leukaemia, and 56 (26.5%) had other malignancies. The main IFI were aspergillosis (n = 107, 50.7%), cryptococcosis (n = 33, 15.6%), PJP (n = 26, 12.3%) and mucormycosis (n = 23, 10.9%). The median delay between the initiation of BTKi and IFI was 2.3, 4.0, 3.0 and 3.0 for aspergillosis, cryptococcosis, PJP and mucormycosis, respectively. The survival rate improved when BTKi was discontinued during infection.

CONCLUSIONS:

Targeted therapies in lymphocytic malignancies raised new issues concerning infectious complications. Monitoring IFI in patients receiving second- and third-generation BTKi is crucial for improving the management of these manifestations.

203

News (Medical) associated with Acalabrutinib

21 Apr 2025

·www.globenewswire.com

Ascentage Pharma Announces Inclusion of Lisaftoclax and Olverembatinib in Chinese Society of Clinical Oncology (CSCO) 2025 Guidelines

ROCKVILLE, Md. and SUZHOU, China, April 21, 2025 (GLOBE NEWSWIRE) -- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for hematological malignancies, today announced that two of its proprietary novel drugs have been included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines. Lisaftoclax (APG-2575), the company’s investigational novel oral Bcl-2 selective inhibitor, received its first recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. Olverembatinib, the company’s novel next-generation tyrosine kinase inhibitor (TKI), received an upgraded recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, and retained its recommendations in the CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies. Bcl-2 inhibitor lisaftoclax (APG-2575) receives its first CSCO Guidelines recommendation As the world’s second Bcl-2 inhibitor to submit a New Drug Application (NDA) and the first China-developed Bcl-2 inhibitor to submit an NDA and receive Priority Review designation in China, lisaftoclax (APG-2575), supported by its robust clinical data, has been recommended in the CSCO 2025 Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies, as a monotherapy for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This is the first CSCO Guidelines recommendation for lisaftoclax (APG-2575), making it the only China-developed Bcl-2 inhibitor recommended in the CSCO Guidelines. This marks a milestone achieved by Ascentage Pharma in advancing the development of this innovative drug to bring meaningful benefit to patients as well as a major breakthrough in the field of hematological malignancies. Prof. Jun Ma, from Harbin Institute of Hematology and Oncology, stated: “These CSCO Guidelines recommendations for lisaftoclax (APG-2575) indicate recognition of the drug’s robust data by a top medical association in China. In the data, lisaftoclax (APG-2575) monotherapy showed a high overall response rate and a fast onset of action that can enable rapid disease control. Moreover, the incidence of tumor-lysis syndrome in patients treated with lisaftoclax (APG-2575) was far lower than was shown in the early data of other Bcl-2 inhibitors, highlighting a favorable tolerability profile that could potentially change the clinical risk management in CLL/SLL. We look forward to lisaftoclax (APG-2575)’s approval in China through the Priority Review pathway, which will bring this innovative therapeutic to patients in need.” In November 2024, the NDA for lisaftoclax (APG-2575) monotherapy for the treatment of R/R CLL/SLL was accepted and granted the Priority Review designation by the Center for Drug Evaluation (CDE) of China National Medical Product Administration (NMPA). Globally, lisaftoclax (APG-2575) is being evaluated in two registrational Phase III studies for the treatment of CLL/SLL, including an international registrational Phase III study of lisaftoclax (APG-2575) combined with a BTK inhibitor in patients with CLL/SLL who had previously received BTK inhibitors (the GLORA Trial); and an international registrational Phase III study evaluating lisaftoclax (APG-2575) combined with acalabrutinib, versus immunochemotherapy in treatment-naïve patients with CLL/SLL (the GLORA-2 Trial). These studies were designed to further broaden the treatment window of lisaftoclax (APG-2575). The first China-approved BCR-ABL inhibitor olverembatinib receives an upgraded recommendation in the CSCO Guidelines In the CSCO 2025 Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, the recommendation for olverembatinib for the treatment of children with Ph+ ALL who harbor the T315I BCR-ABL1 kinase domain mutation was upgraded to Level I, thus opening a whole new chapter for olverembatinib in pediatric hematology. Prof. Xiaofan Zhu, from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, noted, “As a China-developed third-generation TKI, olverembatinib has achieved a major breakthrough in the treatment of children with Ph+ ALL. In the CSCO 2025 Guidelines, the recommendation for olverembatinib in the treatment of patients with Ph+ ALL who harbor the T315I BCR-ABL1 kinase domain mutation or are intolerant to dasatinib has been upgraded to Level I, an update that reflects the drug’s promising clinical utility. Looking ahead, we hope to see more studies further evaluating olverembatinib’s long-term efficacy and searching for more optimized combinations of the drug that can bring greater hope for curative care to children with Ph+ ALL.” In the CSCO 2025 Guidelines for the Diagnosis and Treatment of Hematological Malignancies, olverembatinib retained a number of major recommendations which solidified the drug’s vital role in the treatment of CML. In chronic-phase CML (CML-CP), olverembatinib retained a Level I recommendation for the treatment of all lines of T315I mutant CML-CP; a Level I recommendation for the second-line treatment of patients who had failed first-line treatment with nilotinib or dasatinib and the third-line treatment of patients who are intolerant to and/or failed on two or more TKIs. In progressive-phase CML, olverembatinib retained a Level I recommendation as a treatment option for patients with T315I mutant CML-AP, and those who progressed from CML-CP to CML-AP, or from CML-CP/AP to CML-BP. Moreover, the CSCO 2025 Guidelines emphasized olverembatinib’s advantages in addressing a range of BCR::ABL1 mutations (including T315I, V299L, F317L/V/I/C, T315A, Y253H, E255K/V, and F359C/V/I) and any other mutation (including complex/compound mutations). In Ph+ ALL, olverembatinib has retained its Level I recommendation for response induction and the treatment of relapsed/refractory patients. Olverembatinib is a novel drug developed by Ascentage Pharma with support from China’s National Major New Drug Development Program. As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib is indicated for the treatment of adult patients with TKI-resistant CML-CP or -AP harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. Furthermore, all approved indications of olverembatinib have been included in the China National Reimbursement Drug List (NRDL) which has greatly improved the drug’s accessibility to patients. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics. Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “CSCO Guidelines are among the most recognized clinical guidelines in China, providing crucial guidance to Chinese physicians on the diagnosis and treatment of malignancies. The recommendations for both olverembatinib and lisaftoclax (APG-2575) in the updated guidelines are a testament to our strong and innovative pipeline. In particular, the CSCO Guidelines’ very first recommendations for lisaftoclax (APG-2575), the second Bcl-2 inhibitor to reach NDA submission anywhere in the world, reflect the clinical experts’ forward-looking recognition of this innovative drug, providing much needed new guidance to clinical practices and the answer to a major treatment gap. Meanwhile, we are greatly encouraged by the Guidelines’ upgraded recommendation for olverembatinib in pediatric patients with ALL. In the future, we hope to see additional positive clinical data that can pave the way for upgraded recommendations for these two innovative drugs. We will continue to accelerate the clinical development and commercialization of our drug candidates for the benefit of more patients.” *Lisaftoclax (APG-2575) and olverembatinib are investigational drugs and not yet approved in the US. About Ascentage PharmaAscentage Pharma is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in hematological malignancies. Ascentage Pharma has been listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK since October 2019 and has also been listed on the Nasdaq Global Market under the ticker symbol “AAPG” since January 2025. The company has built a rich pipeline of innovative drug candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53; and next-generation TKIs that target kinase mutants emergent during cancer treatment. Ascentage Pharma is also the only company in the world with active clinical programs targeting all known key apoptosis regulators. Olverembatinib, one of the company’s lead assets, is already approved in China with all of its approved indications included into the China National Reimbursement Drug List (NRDL). Meanwhile, a New Drug Application (NDA) for another one of Ascentage Pharma’s key drug candidates, the novel Bcl-2 selective inhibitor lisaftoclax (APG-2575), has already been accepted and granted the Priority Review designation by the China CDE. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company’s investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfill its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking StatementsThis press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition. These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Special note regarding forward-looking statements and industry data” in its Registration Statement on Form F-1, as amended, filed with the SEC on January 21, 2025 and the Form 20-F filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risk Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited we made or make from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management. As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Contact InformationInvestor Relations:Hogan Wan, Head of IR and StrategyAscentage PharmaHogan.Wan@ascentage.com+86 512 85557777 Stephanie CarringtonICR HealthcareStephanie.Carrington@icrhealthcare.com(646) 277-1282 Media Relations:Sean LeousICR HealthcareSean.Leous@icrhealthcare.com(646) 866-4012

NDAPhase 3Priority ReviewBreakthrough TherapyOrphan Drug

09 Apr 2025

·www.biospace.com

Five Biggest Drug Face-Offs in Pharma History

iStock, leolintang Wegovy and Zepbound are just the latest drug dyads to face-off in the competitive pharma market, continuing a legacy of rivalry that includes blockbuster drugs Keytruda, Humira and Eliquis. Obesity is the most competitive space in biopharma right now. The two frontrunners, Novo Nordisk and Eli Lilly, are locked in a very tight fight for leadership in a market that by some estimates could reach a jaw-dropping $150 billion in the next few years. Novo moved first. Its GLP-1 analog semaglutide was first cleared by the FDA in 2017 as Ozempic for type 2 diabetes. Some four years later, in July 2021, semaglutide won another approval as Wegovy , this time specifically indicated for chronic weight management. Lilly’s weight-loss blockbuster tirzepatide, in comparison, is a relative late-comer, first reaching the U.S. market in 2022 as Mounjaro for type 2 diabetes Then in November 2023, the FDA approved the drug as Zepbound for obesity , setting up the head-to-head battle with Wegovy in the massive and swiftly growing weight loss market. Despite being years behind, Lilly is chipping away at Novo’s lead. Costanza Alciati, pharma analyst at GlobalData, told BioSpace in an email that tirzepatide’s efficacy edge has helped Lilly catch up. Broadly speaking, according to Alciati, the safety profiles of Zepbound and Wegovy are similar, with both drugs sharing common side effects like nausea and vomiting. Both products are also matched in terms of the route and frequency of administration. However, Zepbound’s “weight loss efficacy seems to be higher than Wegovy’s,” Alciati said, adding that “according to trials, there seems to be less muscle mass loss associated with Zepbound’s treatment than Wegovy’s.” Currently, Novo’s first-mover advantage and sprawling global footprint has allowed it to maintain a slight lead over Lilly. Last year, the Danish pharma logged roughly $26 billion in sales for Ozempic and Wegovy worldwide, while Lilly’s tirzepatide franchise brought in nearly $16.5 billion globally. But with an aggressive commercial strategy, Lilly is quickly gaining ground. “Eli Lilly’s drug has now been launched in all major markets,” Alciati said. Last month, the Indianapolis pharma launched Mounjaro in India, beating Novo to tap the market of the world’s most populous country. Aside from Wegovy and Zepbound, pharma has witnessed many other dramatic drug rivalries play out over the years, from Keytruda’s comeback and subsequent dominance over Opdivo and the burgeoning competition between Leqembi and Kisunla. In this article, BioSpace looks at some of the biggest pharma face-offs. Cancer: Merck’s Keytruda vs BMS’ Opdivo In the oncology arena, few drugs can hope to stand up against Merck’s blockbuster PD-1 inhibitor Keytruda, which has become a cornerstone of cancer care since its first approval in September 2014. As of writing, Keytruda has more than 41 approvals under its belt. These include several forms of melanoma, hepatocellular carcinoma, breast cancer and, crucially, lung cancer. For the last two years, it has also been the pharma’s top-selling product , bringing in $29.5 billion in 2024. But it wasn’t always that way. Keytruda once played second fiddle to Bristol Myers Squibb’s PD-1 blocker Opdivo. Approved in December 2014, just months behind Keytruda, Opdivo initially took a sizeable lead in the market, bringing in $942 million in 2015 versus Keytruda’s $566 million. “Initially, Bristol Myers Squibb was dominating that race,” William Blair partner Matt Phipps told BioSpace in an interview last month. “They had broader approvals and bigger indications.” Merck, according to Phipps, “completely overtook” BMS due to better trials and crucial approvals in lung cancer. Opdivo never recovered. Last year, the drug brought in $9.3 billion —less than a third of Keytruda’s sales. Still, BMS continues to carve out a cancer niche for Opdivo. In January, BMS won the race to bring a subcutaneous PD-1 treatment to the market, with the FDA signing off on a new formulation of Opdivo that can be delivered with an injection under the skin. Merck’s application for subcutaneous Keytruda is still under review. Meanwhile, an NSCLC approval in October 2024 made Opdivo the first PD-1 blocker that can be used both before and after surgery. Cardio: BMS, Pfizer’s Eliquis vs Bayer, J&J’s Xarelto Two blood thinners brought by four of the biggest pharmas are battling it out in cardiovascular disease. Bristol Myers Squibb and Pfizer’s oral anticoagulant Eliquis is the stronger competitor. Despite being approved more than a decade ago, Eliquis’ market presence continues to grow, surging 9% year-on-year to bring in $13.3 billion in 2024. Meanwhile, its closest competitor is a distant second. Though it won the FDA’s blessing a year ahead of Eliquis in 2011 , Bayer and Johnson & Johnson’s Xarelto has fallen behind its competitor in terms of market share. The drug peaked in 2021 when it earned J&J $2.44 billion in the U.S. and Bayer just over $5 billion in international markets, for a total of around $7.5 billion. Last year Bayer reported roughly $3.85 billion in international sales for Xarelto, while J&J recorded $2.37 billion in the U.S.—a total of over $6.2 billion. There are likely several reasons for why Eliquis has cleanly outperformed Xarelto, and one of them might be a question of clinical value. A 2021 study published in JAMA showed that in a Medicare population of more than 580,000 patients with atrial fibrillation, Xarelto was associated with significantly elevated risks of major ischemic or hemorrhagic events, such as fatal bleeding, as compared with Eliquis. Total mortality was also worse with Xarelto. Similarly, a 2023 study in Circulation found that Xarelto significantly heightened the risk of ischemic stroke and major bleeding versus Eliquis in patients in the Optum Clinformatics Data Mart database. There have been no well-designed and well-controlled head-to-head trials to compare the drugs. Alzheimer’s: Biogen, Eisai’s Leqembi vs Lilly’s Kisunla Decades of dispiriting clinical failures have finally produced two winners in Alzheimer’s disease. A tough market showdown has followed. In one corner is Biogen and Eisai’s embattled Leqembi and on the other is Eli Lilly’s newer challenger Kisunla. The anti-amyloid antibody Leqembi first won regulatory clearance in January 2023 under the FDA’s accelerated pathway before becoming the industry’s first fully approved Alzheimer’s therapy in July 2023. The buzz around Leqembi was strong, despite questions about the strength of the efficacy results and whether the benefits outweighed the risks. Phase III data presented in September 2022 helped revitalize the anti-amyloid theory, experts said at the time. In June 2023, an FDA advisory committee unanimously endorsed Leqembi’s full approval. Meanwhile, Kisunla’s path to approval was more fraught. In January 2023, the FDA turned down Lilly’s bid for accelerated approval, citing the need for more data from patients who had been treated for at least 12 months. The drug eventually won the regulator’s blessing in July 2024 , almost a year to the day behind Leqembi. Now, however, Leqembi’s edge doesn’t seem so large. Biogen and Eisai have struggled to get the drug off the ground and have been forced at least twice to lower their sales projection for the asset. In March, for instance, Eisai revealed that it expects Leqembi to bring in from ¥250 billion to ¥280 billion (approximately $1.7 billion to $1.9 billion) in its fiscal year 2027—a roughly 50% decline from a prior projection. For fiscal year 2024, which ends this month, the Japanese firm expects full-year sales of around $280 million for Leqembi. Lilly has already launched Kisunla in the U.S. but has yet to report sales figures. But both drugs have faced concerns about side effects called ARIA, which can signal bleeding or swelling in the brain. They have also faced slow uptake as physicians and health systems struggle to adapt to the new treatment paradigm. I&I: AbbVie’s Humira vs J&J’s Stelara Two pharma giants are duking it out in the immunology space with blockbuster drugs that are past their prime. AbbVie’s Humira was for six straight years the world’s best-selling drug. The biologic peaked in 2022 , bringing in $21.2 billion. But since losing key patent protections in 2023, its sales have declined steeply : last year, Humira made just under $9 billion . On the other hand, J&J’s Stelara never reached the same sales heights as Humira. At its peak in 2023, Stelara raked in $10.86 billion before dipping 4.6% to $10.34 billion last year. Like AbbVie’s biologic, Stelara is contending with copycat competitors. After it lost market exclusivity in 2023, several biosimilars have entered the U.S. market, including Amgen’s Wezlana and Sandoz’s Pyzchiva . Both Humira and Stelara work by tamping down the inflammatory response and share a substantial overlap in their indications, including psoriatic arthritis, plaque psoriasis, Crohn’s disease and ulcerative colitis. The specific mechanisms by which the drugs exert their therapeutic effects differ, however. Humira targets TNF-alpha, while Stelara acts on IL-12 and IL-23. All three molecules are crucial parts of the inflammatory cascade and often act synergistically, with slight differences in functionality. IL-12 and IL-23 explicitly encourage inflammation, for instance, while TNF-alpha can have both pro- and anti-inflammatory effects. In May 2021, a head-to-head study showed that despite these mechanistic nuances, Stelara and Humira are largely clinically similar. In patients with Crohn’s disease, Stelara induced a 64.9% clinical remission rate at 52 weeks, while Humira achieved a 61% remission rate at the same time point—a difference that failed to reach statistical significance. Lymphoma: AstraZeneca’s Calquence vs AbbVie’s, J&J’s Imbruvica The blood cancer field is witness to a BTK inhibitor battle between AbbVie and J&J’s Imbruvica, the first-comer, and AstraZeneca’s Calquence, which entered the ring four years later. The bad blood between the two goes way back to the biotech days, when Pharmacyclics developed what would become Imbruvica and rival Acerta Pharma championed Calquence. The rivalry was chronicled in Nathan Vardi’s book For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug . Both drugs work by blocking the Bruton’s tyrosine kinase, an enzyme that plays a crucial signaling role in the proliferation and activity of B cells. Because they share a mechanism of action, the two products also have wide overlap in their indications. Imbruvica and Calquence are both approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). Currently, Imbruvica has a slight edge. Last year, AbbVie reported nearly $3.35 billion in worldwide sales for the drug, as opposed to Calquence’s $3.13 billion. Imbruvica also has broader coverage: Aside from the indications that it shares with Calquence, it is also approved for chronic graft versus host disease and the rare blood cancer Waldenström’s macroglobulinemia. But Calquence is quickly gaining ground. In 2024, AstraZeneca’s asset grew 24% year-on-year, while Imbruvica slid 6.9%. Calquence is also catching up clinically. A May 2024 readout showed that AstraZeneca’s drug, when combined with standard chemoimmunotherapy, can boost progression-free survival in untreated patients with mantle cell lymphoma (MCL). AbbVie and J&J had pulled Imbruvica’s accelerated approval in this indication nearly a year before. Calquence remains approved for MCL under the FDA’s accelerated pathway. Meanwhile, real-world data presented at the 2024 Congress of the European Hematology Association showed that patients with CLL or SLL who were treated with Calquence had longer time to discontinuation or death than comparators on Imbruvica. Time to next treatment was also longer in the Calquence group, as reported by OncLive at the time.

Drug ApprovalClinical ResultPhase 3Immunotherapy

31 Mar 2025

·www.astrazeneca.com

Calquence plus chemoimmunotherapy recommended for approval in the EU by CHMP as first and only BTK inhibitor for 1st-line mantle cell lymphoma

AstraZeneca’s Calquence (acalabrutinib) in combination with bendamustine and rituximab has been recommended for approval in the European Union (EU) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous hematopoietic stem cell transplantation. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the ECHO Phase III trial which were presented at the European Hematology Association 2024 Congress. Results from the ECHO trial showed Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). Median progression-free survival (PFS) was 66.4 months for patients treated with the Calquence combination versus 49.6 with chemoimmunotherapy alone. This recommendation for Calquence as a combination treatment in the 1st-line MCL setting follows the recent CHMP positive opinion for Calquence as a monotherapy for the treatment of adult patients with relapsed or refractory MCL. Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich, and investigator in the trial, said: "Results from the pivotal ECHO trial demonstrated the significant benefits of the Calquence combination in managing this rare and aggressive cancer. Today’s recommendation is an important advance within the mantle cell lymphoma first-line treatment landscape, especially for older patients who need a balance of efficacy and tolerability.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Today's positive recommendation from the CHMP further reinforces the potential of Calquence to advance first-line treatment options in mantle cell lymphoma, with the Calquence combination demonstrating an almost one and a half year improvement in progression-free survival in this setting. If approved, Calquence has the potential to transform the standard of care as the first BTK inhibitor approved for these patients in Europe.” MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often diagnosed at an advanced stage.1,2 It is estimated that more than 6,000 patients were diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.3 The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified. Calquence plus bendamustine and rituximab is approved in the US and several other countries in this setting based on the ECHO results. Regulatory applications are currently under review in Japan and several other countries in this indication. Notes Mantle cell lymphoma (MCL) While MCL patients initially respond to treatment, patients do tend to relapse.4 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; It is estimated that there are more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan and China.3,4,5 ECHO ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL.6 Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.6 The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR) and time to response (TTR).6 The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.6 The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.6,7,8 Calquence Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion. Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL. Calquence is also approved for the treatment of adult patients with previously untreated MCL in the US and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in the US, China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan. As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma. AstraZeneca in haematology AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians. In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Adrian Kemp Company Secretary AstraZeneca PLC Oncology Corporate and financial

Clinical ResultImmunotherapyPhase 3Drug Approval

100 Deals associated with Acalabrutinib

External Link

KEGG	Wiki	ATC	Drug Bank
D10893	Acalabrutinib	L01XE51	DB11703

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Small Lymphocytic Lymphoma	United States	AstraZeneca UK Ltd.	21 Nov 2019
Chronic Lymphocytic Leukemia	Canada	AstraZeneca Canada, Inc.	02 Oct 2019
Mantle-Cell Lymphoma	United States	AstraZeneca UK Ltd.	31 Oct 2017

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Mantle cell lymphoma recurrent	NDA/BLA	China	AstraZeneca AB	27 Feb 2025
Mantle cell lymphoma refractory	NDA/BLA	China	AstraZeneca AB	27 Feb 2025
Large B-cell lymphoma	Phase 3	Germany	AstraZeneca PLC	07 Jun 2023
Recurrent Chronic Lymphoid Leukemia	Phase 3	Germany	AstraZeneca PLC	19 Apr 2022
Diffuse Large B-Cell Lymphoma	Phase 3	United States	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	China	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	Japan	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	Australia	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	Austria	AstraZeneca PLC	08 Oct 2020
Diffuse Large B-Cell Lymphoma	Phase 3	Belgium	AstraZeneca PLC	08 Oct 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03932331 (CTgov)	Phase 1/2	Chronic Lymphocytic Leukemia \| Mantle cell lymphoma refractory	105	acalabrutinib (Phase I)	mogatixiwz = kyctvtdnyb tfwxvpawuj (cvgpkhckwn, keldakbrcm - ydjdbaanaa) View more	-	20 Mar 2025
				acalabrutinib (Phase II MCL)	hkxhddsotl = abtbomsrss riqpgwshgj (ukpicjrosx, qvweyjiwag - lldbkmbezq) View more
NCT03836261 (NEWS \| Pubmed) Manual	Phase 3	Chronic Lymphocytic Leukemia First line	867	Acalabrutinib-Venetoclax	vgdzsebiiu(yyxxjlhtxz) = lqbtcnziom nhympjvfmb (nimibrozek ) View more	Positive	21 Feb 2025
				Acalabrutinib-Venetoclax-Obinutuzumab	vgdzsebiiu(yyxxjlhtxz) = okklhhjmuk nhympjvfmb (nimibrozek ) View more
NCT03836261 (AMPLIFY, Pubmed \| N Engl J Med)	Phase 3	Chronic Lymphocytic Leukemia 17p deletion \| IGHV	867	Acalabrutinib-Venetoclax	hifepcgjpa(cryrcwvuur) = death from coronavirus disease 2019 was reported in 10, 25, and 21 patients in the three groups mvfrgalzxy (qcjznhhtes ) View more	Positive	20 Feb 2025
				Acalabrutinib-Venetoclax-Obinutuzumab
NCT04075292 (CTgov)	Phase 3	Chronic Lymphocytic Leukemia	155	Acalabrutinib	nrncyouyhf(mchghxcsue) = ctjideaorq nnexskrtca (xtyqzjsqnk, flqflvhpuw - vlhqnmqvag) View more	-	30 Jan 2025
NCT03571568 (Company_Website) Manual	Phase 2	Non-Hodgkin Lymphoma	2	BI-1206 + rituximab + Calquence	npynspfnam(dpvfprxzji) = uihmupdzvu rcyxkmbudr (enkcdsgbnj ) View more	Positive	08 Jan 2025
NCT04462328 (ASH2024) Manual	Phase 1	Primary Central Nervous System Lymphoma	13	Acalabrutinib 100 mg BID + DurvalumabDurvalumab 1500 mg IV	eqdlquudlc(bdtvzhlvnj) = fwcplapkho jjmwmtxxwp (yuqjykhxym ) View more	Positive	09 Dec 2024
NCT03836261 (AMPLIFY, ASH2024) Manual	Phase 3	Chronic Lymphocytic Leukemia First line	867	Acalabrutinib + Venetoclax	ewqhnriyhf(urkrtlccaz) = iyucvswtzm fjzvjxwktp (cxvjoyztas ) View more	Positive	09 Dec 2024
				Acalabrutinib + Venetoclax + Obinutuzumab	ewqhnriyhf(urkrtlccaz) = jppplogqrt fjzvjxwktp (cxvjoyztas ) View more
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib 100 mg BID + Rituximab 375 mg/m2 IV	dfcbwbfngg(ebmaeomuoh) = grade 3-4 AE were cardiovascular toxicity in 7 pts textdpiyec (scbuqdlcjs ) View more	-	09 Dec 2024
ASH2024	Not Applicable	Mantle-Cell Lymphoma	-	Acalabrutinib	phoylfsnrq(uorbypzkvh) = 16% gezflxeezh (lopjkjryma ) View more	-	09 Dec 2024
				Venetoclax
ASH2024	Not Applicable	Diffuse Large B-Cell Lymphoma	-	RICE-A + Acalabrutinib 100mg BID	mhltaaykpz(wcvrhxyajx) = Gastrointestinal AEs were observed in 5 patients (4 Grade1/2 and 1 Grade3/4) jzdkkasvei (wibqckocnh ) View more	-	08 Dec 2024

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